Genetic determinants of "innate" T lymphocytes development and homeostasis

项目摘要 先天的 传统型 他们的 要求 也就是说， 分子， 这个 不确定。 系统， 多态 映射 资源 发展 一个 变异 使用 T细胞是一组不同种类的αβ和γδT细胞，它们的反应速度比 T细胞被激活。这种快速响应反映了他们在 胸腺的发育。这些先天T细胞也共享非MHC I或II类限制 用于抗原识别。先天T细胞组中的三个主要群体被识别， 识别非多态CD1d糖脂抗原的不变NKT细胞 粘膜相关不变T细胞(MAIT)识别由 非多态的MR1分子，以及仍具有抗原特异性的Gamma Delta T细胞 总之，这些先天T细胞充当了先天免疫和获得性免疫之间的桥梁 对免疫调节和宿主保护有很大贡献。感谢主持人扮演的角色 在先天T细胞的稳态发育和动态平衡中的作用，我们建议利用QTL 在合作杂交和多样性杂交(DO)小鼠中。这些遗传多样性的小鼠 提供强大的实验系统来测试先天T细胞的变异 而动态平衡是由基因控制的，并绘制了多样性的来源。我们将进行 先天T细胞CC和DO菌株的综合筛选以评估遗传多样性 (目标1)。然后，我们将确定导致先天T细胞发育/内稳态变异的基因 QTL定位(目标2)。 D H 鉴于它们有能力将先天和适应性的关键炎症轴联系起来 免疫，更好地了解支持先天T细胞发育和可塑性的分子基础， 而这一特征在多大程度上解释了它们的病理生理作用，对于开发新的 治疗方法。

Project Summary Innate conventional their requirement namely, molecules, the uncertain. systems, polymorphism mapping resources development a variation using T cells are a heterogeneous group of αβ and γδ T cells that respond much more r apidly than T cells upon activation. This swiftness of response r eflects their acquisition of functionality during development in the thymus. These innate T cells also share a non-MHC class I or II restriction for antigen recognition. Three major populations within the innate T cell group are recognized, the invariant NKT cells that recognize glycolipid antigens presented by non-polymorphic CD1d the mucosal associated invariant T (MAIT) cells t hat recognize vitamin metabolites presented by non-polymorphic MR1 molecules, and the gamma delta T cells which antigen specificities remain Altogether, these innate T cells, acting as bridges between the innate and adaptive immune contribute greatly to immune regulation and host protection. To appreciate the role that host play in steady-state evelopment and homeostasis of innate T cells, we propose to use QTL in the Collaborative Cross and Diversity Outbred (DO) mice. These genetically diverse mouse provide powerful experimental systems to test the ypothesis that variation in innate T cell and homeostasis is genetically regulated and to map the source of the diversity. We will conduct comprehensive screen of CC and DO strains for innate T cells to estimate the diversity resulting from genetic (Aim 1). We will then identify genes that underlie variation in innate T cell development/homeostasis QTL mapping (Aim 2). d h Given their capacity to link key inflammatory axes of innate and adaptive immunity, a better understanding of the molecular basis underpinning innate T cell development and plasticity, and how much this feature accounts for their pathophysiological roles, is critical for developing novel therapeutic approaches.